John A. Weigelt

Linezolid versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections

ABSTRACT Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P = 0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P < 0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA.

Improved predictions from a severity characterization of trauma (ASCOT) over Trauma and Injury Severity Score (TRISS): results of an independent evaluation

OBJECTIVE In 1986, data from 25,000 major trauma outcome study patients were used to relate Trauma and Injury Severity Score (TRISS) values to survival probability. The resulting norms have been widely used. Motivated by TRISS limitations, A Severity Characterization of Trauma (ASCOT) was introduced in 1990. The objective of this study was to evaluate and compare TRISS and ASCOT probability predictions using carefully collected and independently reviewed data not used in the development of those norms. DESIGN This was a prospective data collection for consecutive admissions to four level I trauma centers participating in a major trauma outcome study. MATERIALS AND METHODS Data from 14,296 patients admitted to the four study sites between October 1987 through 1989 were used. The indices were evaluated using measures of discrimination (disparity, sensitivity, specificity, misclassification rate, and area under the receiver-operating characteristic curve) and calibration [Hosmer-Lemeshow goodness-of-fit statistic (H-L)]. MEASUREMENTS AND MAIN RESULTS For blunt-injured adults, ASCOT has higher sensitivity than TRISS (69.3 vs. 64.3) and meets the criterion for model calibration (H-L statistic < 15.5) needed for accurate z and W scores. The TRISS does not meet the calibration criterion (H-L = 30.7). For adults with penetrating injury, ASCOT has a substantially lower H-L value than TRISS (20.3 vs. 138.4), but neither meets the criterion. Areas under TRISS and ASCOT ROC curves are not significantly different and exceed 0.91 for blunt-injured adults and 0.95 for adults with penetrating injury. For pediatric patients, TRISS and ASCOT sensitivities (near 77%) and areas under receiver-operating characteristic curves (both exceed 0.96) are comparable, and both models satisfy the H-L criterion. CONCLUSIONS In this age of health care decisions influenced by outcome evaluations, ASCOTs more precise description of anatomic injury and its improved calibration with actual outcomes argue for its adoption as the standard method for outcome prediction.

Complications of negative laparotomy for trauma

Controversy continues about how often a negative laparotomy should be accepted in the management of patients with blunt and penetrating trauma. A key issue is the complications, especially small bowel obstruction. To define these complications, the charts of 248 patients who underwent negative laparotomy for trauma were examined. There were 185 patients with penetrating injuries and 63 with blunt injuries. Associated injuries were present in 119 patients. Acute perioperative morbidity occurred in 53 percent of the patients with associated injuries and 22 percent of patients with no associated injuries. On long-term follow-up, five patients developed small bowel obstructions. The incidence of small bowel obstruction was related to operative exposure. We have concluded that early morbidity after a negative laparotomy is more common when associated injuries are present. The risk of postoperative small bowel obstruction is small, especially when extensive operative dissection is not necessary. Abdominal exploration should not be discarded as a viable diagnostic and therapeutic procedure in patients with equivocal findings.

Evaluation of computed tomography and diagnostic peritoneal lavage in blunt abdominal trauma

Three hundred one hemodynamically stable patients with equivocal abdominal examinations following blunt abdominal trauma had a CT scan followed by DPL. Both studies were negative in 194 patients (71.6%) and positive in 51 patients (27.1%). Seven of the 51 patients (13.7%) had an additional significant injury at operation that was not seen on the CT scan. Nineteen patients had a negative CT scan, a positive DPL, and a significant injury confirmed at celiotomy. In this group of 19 patients, the CT failed to identify seven splenic, three hepatic, and three small bowel injuries. There were two complications attributed to DPL. Three patients had a false negative DPL. Diagnostic peritoneal lavage continues to be a reliable study (sensitivity--95.9%, specificity--99%, accuracy--98.2%). The CT scan is not as sensitive (sensitivity--74.3%, p less than 0.001; specificity--99.5%, accuracy--92.6%). It is concluded that selective use of both procedures is appropriate as long as one recognizes the inherent limitations of each.

Skin, Soft Tissue, Bone, and Joint Infections in Hospitalized Patients: Epidemiology and Microbiological, Clinical, and Economic Outcomes

BACKGROUND Infections involving skin, soft tissue, bone, or joint (SSTBJ) are common and often require hospitalization. There are currently few published studies on the epidemiology and clinical and economic outcomes of these infections, whether acquired in the community or healthcare setting, in a large population. OBJECTIVE To characterize outcomes of culture-proven SSTBJ infection in hospitalized patients, using information from a large database. DESIGN We identified patients hospitalized in 134 institutions during 2002-2003 for whom specific International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes and a culture-positive SSTBJ specimen were recorded. Patients were classified into 4 clinical groups based on the type and clinical severity of infection. Patients in each group were further classified on the basis of whether their infection was community acquired or healthcare associated and whether it was complicated or uncomplicated. RESULTS We identified 12,506 patients with culture-positive infections and categorized them as having cellulitis (37.3%), osteomyelitis or septic arthritis (22.4%), surgical wound infection (26.1%), device-associated or prosthesis infection (7.2%), or other SSTBJ infection (6.9%). Monomicrobial infection was reported for 59% of patients, 54.6% of whom had Staphylococcus aureus as the etiologic agent. Of all S. aureus isolates recovered, 1,121 (28.0%) of 4,007 were resistant to methicillin. Healthcare-associated infections accounted for 27.2% of cases and were associated with a significantly greater mortality rate, a longer length of stay, and greater hospital charges, compared with community-acquired infections. Patients with a complicated infection (78.4%) had a significantly greater mortality rate, a longer length of stay, and greater hospital charges, compared with patients with an uncomplicated infection. CONCLUSIONS SSTBJ infections are frequent among hospitalized patients. S. aureus caused infection in more than 50% of the patients studied, and 28.0% of the S. aureus isolates recovered were resistant to methicillin. Healthcare-associated and complicated infections are associated with a significantly higher mortality rate and more prolonged and expensive hospitalizations. These findings could assist in projects to revise current management strategies in order to optimize outcomes while restraining costs.

Treatment of Occult Pneumothoraces from Blunt Trauma

BACKGROUND Occult pneumothoraces (OPTXs) are seen on abdominal computed tomographic (CT) scans but not on routine chest x-ray films. Optimal treatment for blunt trauma OPTXs has not been defined. We hypothesized that OPTXs could be safely observed without need for a chest tube (CT). METHODS A prospective trial randomized blunt trauma patients with OPTXs to CT scan or observation. Patients were not excluded for positive pressure ventilation. Primary outcome measures were respiratory distress and pneumothoraces progression. RESULTS Thirty-nine patients with 44 pneumothoraces were enrolled. Eighteen patients received a CT scan, and 21 patients were observed. Nine patients in each group received positive pressure ventilation. There was no difference in overall complication rate. No patient had respiratory distress related to the OPTX or required emergent CT scan. CONCLUSIONS Observation of OPTX is not associated with an increased incidence of pneumothorax progression or respiratory distress. These pneumothoraces can be safely observed in patients with blunt trauma injury regardless of the need for positive pressure ventilation.

Efficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft-tissue infections proven to be caused by methicillin-resistant Staphylococcus aureus.

BACKGROUND This open-label study compared oral or intravenous linezolid with intravenous vancomycin for treatment of complicated skin and soft-tissue infections (cSSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA). METHODS Patients with proven MRSA cSSTI were randomized to receive linezolid or vancomycin. Clinical and microbiologic outcomes, duration of antimicrobial therapy, length of hospital stay, and safety were assessed. RESULTS In the per-protocol population, the rate of clinical success was similar in linezolid- and vancomycin-treated patients (P = .249). The rate of success was significantly higher in linezolid-treated patients in the modified intent-to-treat population (P = .048). The microbiologic success rate was higher for linezolid at the end of treatment (P < .001) and was similar at the end of the study (P = .127). Patients receiving linezolid had a significantly shorter length of stay and duration of intravenous therapy than patients receiving vancomycin. Both agents were well tolerated. Adverse events were similar to each drugs established safety profile. CONCLUSIONS Linezolid is an effective alternative to vancomycin for the treatment of cSSTI caused by MRSA.

Surgical site infections: Causative pathogens and associated outcomes.

BACKGROUND Surgical site infections (SSIs) are associated with substantial morbidity, mortality, and cost. Few studies have examined the causative pathogens, mortality, and economic burden among patients rehospitalized for SSIs. METHODS From 2003 to 2007, 8302 patients were readmitted to 97 US hospitals with a culture-confirmed SSI. We analyzed the causative pathogens and their associations with in-hospital mortality, length of stay (LOS), and cost. RESULTS The proportion of methicillin-resistant Staphylococcus aureus (MRSA) significantly increased among culture-positive SSI patients during the study period (16.1% to 20.6%, respectively, P < .0001). MRSA (compared with other) infections had higher raw mortality rates (1.4% vs 0.8%, respectively, P=.03), longer LOS (median, 6 vs 5 days, respectively, P < .0001), and higher hospital costs (

Forty-three cases of vertebral artery trauma.

7036 vs

Effect of preinjury illness on trauma patient survival outcome.

6134, respectively, P < .0001). The MRSA infection risk-adjusted attributable LOS increase was 0.93 days (95% confidence interval [CI]: 0.65-1.21; P < .0001), and cost increase was